Behavioral, biochemical and pharmacological studies of active avoidance behavior suggest the existence of basic arousal and suppressive systems which control behavior in these situations. Furthermore, data indicate that the cholinergic system is involved in mediating behavioral suppression. Detailed studies of the cholinergic system in two strains of rats which display opposite behavior in their immediate response (one strain becomes active, the other strain becomes suppressed) and in their delayed response to shock-stress (Kamin effect) will be continued to further establish biochemical correlated in, and anatomical locations of the cholinergic systems which are involved in mediating this differential behavior. Experiments will also be undertaken to investigate the hypothesis that the cholinergically mediated suppressive system is in functional balance with a catecholaminergically mediated arousal system and to determine the role of TRH in controlling these sytems. Because of the complicated nature of cholinergic system, its function will be evaluated by measuring a number of parameters rather than relying on a single measure (ACh turnover by two independent methods, high affinity choline uptake, postsynaptic receptor sensitivity). The studies will also involve microinjection of cholinergic agonists and antagonists into, and lesions of specific brain areas in conjunction with measurement of active avoidance behavior to further characterize the system. Though there is some difficulty in extrapolating behavior from animal models to man, the balance between arousal and suppression may also govern basic behavioral patterns in humans. Biochemical defects which occur in these regulatory systems might then contribute to various forms of maladaptive social behavior in response to environment stimuli. Therefore, a more complete understanding of the role of the cholinergic system in mediating suppressive behavior in animals will further our understanding of the biochemical basis behavioral system which may be of importance in human behavior.